Efficacy of Oral Encochleated Amphotericin B in a Mouse Model of Cryptococcal Meningoencephalitis.

Cryptococcus neoformans is an encapsulated yeast responsible for approximately a quarter of a million deaths worldwide annually despite therapy, and upwards of 11% of HIV/AIDS-related deaths, rivaling the impact of tuberculosis and malaria. However, the most effective antifungal agent, amphotericin B, requires intravenous delivery and has significant renal and hematopoietic toxicity, making it difficult to utilize, especially in resource-limited settings. The present studies describe a new nanoparticle crystal encapsulated formulation of amphotericin B known as encochleated amphotericin B (CAmB) that seeks to provide an oral formulation that is low in toxicity and cost. Using a 3-day delayed model of murine cryptococcal meningoencephalitis and a large inoculum of a highly virulent strain of serotype A C. neoformans, CAmB, in combination with flucytosine, was found to have efficacy equivalent to parental amphotericin B deoxycholate with flucytosine and superior to oral fluconazole without untoward toxicity. Transport of fluorescent CAmB particles to brain as well as significant brain levels of amphotericin drug was demonstrated in treated mice, and immunological profiles were similar to those of mice treated with conventional amphotericin B. Additional toxicity studies using a standardized rat model showed negligible toxicity after a 28-day treatment schedule. These studies thus offer the potential for an efficacious oral formulation of a known fungicidal drug against intrathecal cryptococcal disease.IMPORTANCECryptococcus neoformans is a significant global fungal pathogen that kills an estimated quarter of a million HIV-infected individuals yearly and has poor outcomes despite therapy. The most effective therapy, amphotericin B, is highly effective in killing the fungus but is available only in highly toxic, intravenous formulations that are unavailable in most of the developing world, where cryptococcal disease in most prevalent. For example, in Ethiopia, reliance on the orally available antifungal fluconazole results in high mortality, even when initiated as preemptive therapy at the time of HIV diagnosis. Thus, alternative agents could result in significant saving of lives. Toward this end, the present work describes the development of a new formulation of amphotericin B (CAmB) that encapsulates the drug as a crystal lipid nanoparticle that facilitates oral absorption and prevents toxicity. Successful oral absorption of the drug was demonstrated in a mouse model that, in combination with the antifungal flucytosine, provided efficacy equal to a parental preparation of amphotericin B plus flucytosine. These studies demonstrate the potential for CAmB in combination with flucytosine to provide an effective oral formulation of a well-known, potent fungicidal drug combination.

Macrolide therapy of group A streptococcal pharyngitis: 10 days of macrolide therapy (clarithromycin) is more effective in streptococcal eradication than 5 days (azithromycin).

We compared recommended doses of 2 oral macrolide antibiotics (10 days of clarithromycin, 5 days of azithromycin) for eradicating group A streptococci from the throats of individuals aged > or = 12 years with symptomatic pharyngitis and a positive throat culture. Patients received either clarithromycin (250 mg b.i.d. for 10 days [n=260]) or azythromycin (500 mg on day 1, followed by 250 mg q.d. for 4 days [n=265]). Follow-up throat cultures were obtained both at 13--19 days and at 28--38 days. We evaluated 392 patients (median age, 26 years; clarithromycin, 194 patients; azyithromycin, 198 patients). Ten days of clarithromycin therapy was more effective than 5 days of azithromycin therapy in eradicating the organism (91% [176/194] vs. 82% [162/198]; P=.012). More than 97% of all streptococcal isolates were macrolide-sensitive. Whether these bacteriologic eradication rates were the result of the 2 macrolides compared or were due to differences in duration of therapy could not be determined, but the statistically significant difference in eradication of group A streptococci does raise additional questions about shortened courses of macrolide therapy for this common infection.

Ketolide ABT-773 is active against Toxoplasma gondii.

ABT-773 is active in vitro and in vivo against Toxoplasma gondii. It inhibited replication of RH strain tachyzoites in human foreskin fibroblasts. Mice infected intraperitoneally with tachyzoites and treated orally with 25, 50 or 100 mg/kg/day of ABT-773 for 10 days had 20% (P: = 0.016), 50% (P: = 0.003) and 100% (P: = 0.001) survival, respectively. Remarkable and highly significant survival was also noted in mice infected orally with strain C56 cysts and treated with ABT-773. Thus, ABT-773 may be useful for therapy of human toxoplasmosis.

Dialectical behavior therapy for patients with borderline personality disorder and drug-dependence.

A randomized clinical trial was conducted to evaluate whether Dialectical Behavior Therapy (DBT), an effective cognitive-behavioral treatment for suicidal individuals with borderline personality disorder (BPD), would also be effective for drug-dependent women with BPD when compared with treatment-as-usual (TAU) in the community. Subjects were randomly assigned to either DBT or TAU for a year of treatment. Subjects were assessed at 4, 8, and 12 months, and at a 16-month follow-up. Subjects assigned to DBT had significantly greater reductions in drug abuse measured both by structured interviews and urinalyses throughout the treatment year and at follow-up than did subjects assigned to TAU. DBT also maintained subjects in treatment better than did TAU, and subjects assigned to DBT had significantly greater gains in global and social adjustment at follow-up than did those assigned to TAU. DBT has been shown to be more effective than treatment-as-usual in treating drug abuse in this study, providing more support for DBT as an effective treatment for severely dysfunctional BPD patients across a range of presenting problems.

Clarithromycin resistance and susceptibility patterns of Mycobacterium avium strains isolated during prophylaxis for disseminated infection in patients with AIDS.

A randomized, placebo-controlled trial was conducted to evaluate the efficacy of clarithromycin in the prevention of disseminated Mycobacterium avium complex (MAC) infection in patients with AIDS; special attention was given to the development of clarithromycin resistance. The median time to documented MAC bacteremia was 199 days for placebo-treated patients, 217 days for clarithromycin-treated patients infected with clarithromycin-susceptible MAC, and 385 days for clarithromycin-treated patients infected with clarithromycin-resistant MAC. Most of the patients with clarithromycin-resistant isolates (91%) had a baseline CD4 T-cell count of < 20/microL, while these low counts occurred in only 25% of patients having clarithromycin-susceptible breakthrough isolates. The emergence of clarithromycin resistance did not affect the total period of survival. Resistance to clarithromycin in breakthrough MAC isolates emerges most likely when the patient is extremely immunodeficient at the time of initiation of the preventative therapy.

Steady-state pharmacokinetics and electrocardiographic pharmacodynamics of clarithromycin and loratadine after individual or concomitant administration.

To evaluate the potential for an interaction between clarithromycin and loratadine, healthy male volunteers (n = 24) received each of the following regimens according to a randomized crossover design: 500 mg of clarithromycin orally every 12 h (q12h) for 10 days, 10 mg of loratadine orally q24h for 10 days, and the combination of clarithromycin and loratadine. A washout interval of 14 days separated regimens. The addition of loratadine did not statistically significantly affect the steady-state pharmacokinetics of clarithromycin or its active metabolite, 14(R)-hydroxy-clarithromycin. However, the addition of clarithromycin statistically significantly altered the steady-state maximum observed plasma concentration and the area under the plasma concentration-time curve over a dosing interval for loratadine (+36 and +76%, respectively) and for descarboethoxyloratadine (DCL), the active metabolite of loratadine (+69 and +49%, respectively). Clarithromycin probably inhibits the oxidative metabolism of loratadine and DCL by the cytochrome P-450 3A subfamily. Electrocardiograms (n = 12) were obtained over 24-h periods at baseline and steady state (day 10). The mean maximum QTc interval and area under the QTc interval-time curve on day 10 were modestly increased (<3%) from baseline for all three regimens, but no QTc interval exceeded 439 ms for any subject. Elevated steady-state concentrations of loratadine and DCL do not appear to be associated with adverse cardiovascular effects related to prolongation of the QTc interval. Loratadine and clarithromycin were well tolerated, alone and in combination.

Clarithromycin and ethambutol with or without clofazimine for the treatment of bacteremic Mycobacterium avium complex disease in patients with HIV infection.

OBJECTIVE: To compare the efficacy of two- and three-drug regimens for treating Mycobacterium avium complex (MAC) bacteremia in patients with AIDS. DESIGN: Randomized open-label clinical trial. SETTING: Outpatient HIV specialty centers' clinics. PATIENTS: A total of 106 adults with AIDS and MAC bacteremia. INTERVENTIONS: Patients were treated with clarithromycin 500 mg twice daily and ethambutol 800-1,000 mg daily and were randomized to receive clofazimine 100 mg daily or no clofazimine. MAIN OUTCOME MEASURES: Quantitative blood MAC cultures, symptoms, adverse reactions and survival. RESULTS: Patients randomly assigned to three drugs had significantly higher baseline colony counts of MAC in blood than patients receiving two drugs. The proportion of patients becoming culture-negative was 65% in the two-drug group and 54% in the three-drug group. The median time to negative culture was 58 days for patients in the two-drug and 63 days for the three-drug group. At the last visit during treatment, the mean reduction in colony forming units/ml of MAC in blood was 1.8 log10 for the two-drug group and 2.3 log10 for the three-drug group. Improvement in fever and night sweats was reported by 87 and 89% of the two-drug patients and 84 and 86% of the three-drug patients. During the study, 38% of two-drug patients and 61% of three-drug patients died (P = 0.032), and time to death was shorter in patients treated with three drugs (P = 0.012). In a multivariate analysis, both assignment to clofazimine and high baseline colony counts of MAC bacteremia were significantly associated with death (P < 0.05). CONCLUSION: The addition of clofazimine to a regimen of clarithromycin and ethambutol for MAC bacteremia in AIDS patients does not contribute to clinical response and is associated with higher mortality.

Ancillary benefits of Mycobacterium avium-intracellulare complex prophylaxis with clarithromycin in HIV-infected patients.

Because of the significant morbidity and mortality associated with opportunistic infections, prophylaxis has become routine practice in the management of immunocompromised patients such as those with AIDS. Clarithromycin, an antimicrobial agent with a broad spectrum of activity against most common respiratory pathogens as well as many protozoa, has proven to be effective for both treatment and prophylaxis of Mycobacterium avium-intracellulare complex (MAC) infection in AIDS patients. Results of a large multinational placebo-controlled study suggest that clarithromycin for MAC prophylaxis provides additional benefits. In this study, clarithromycin statistically significantly reduced the incidence of Pneumocystis carinii pneumonia (5.3% of clarithromycin recipients vs 10.0% of placebo recipients; p = 0.021), community-acquired pneumonia (7.1 vs 13.0%; p = 0.010), Giardia lamblia infection (0.9 vs 2.9%; p = 0.048), and neoplastic diseases (1.8 vs 4.1%; p = 0.010) in AIDS patients with CD4+ counts of < or = 100 cells/microliter.

A randomized trial of clarithromycin as prophylaxis against disseminated Mycobacterium avium complex infection in patients with advanced acquired immunodeficiency syndrome.

BACKGROUND: Disseminated infection with Mycobacterium avium complex is the most common opportunistic infection in patients with advanced stages of the acquired immunodeficiency syndrome (AIDS). We studied the efficacy and safety of prophylactic treatment with clarithromycin, a macrolide antibiotic. METHODS: We conducted a randomized, placebo-controlled, double-blind study of clarithromycin in patients with AIDS in the United States and Europe. Entry criteria included blood cultures that were negative for M. avium complex, a Karnofsky performance score of 50 or higher, a CD4 cell count of 100 or less per cubic millimeter, and a life expectancy of at least six months. RESULTS: After the first interim analysis, the study was stopped. M. avium complex infection developed in 19 of the 333 patients (6 percent) assigned to clarithromycin and in 53 of the 334 (16 percent) assigned to placebo (adjusted hazard ratio, 0.31; 95 percent confidence interval, 0.18 to 0.53; P<0.001). During the follow-up period of about 10 months, 32 percent of the patients in the clarithromycin group died and 41 percent of those in the placebo group died (hazard ratio, 0.75; P=0.026). In the clarithromycin group, isolates from 11 of the 19 patients with M. avium complex infection were resistant to clarithromycin. Prophylaxis with clarithromycin was associated with an increased incidence of taste perversion (11 percent in the clarithromycin group vs. 2 percent in the placebo group, P<0.001) and rectal disorders (8 percent vs. 3 percent, P = 0.007); however, the frequency of more severe adverse events was similar in the two groups (7 percent and 6 percent, respectively). CONCLUSIONS: In patients with advanced AIDS, the prophylactic administration of clarithromycin is well tolerated, prevents M. avium complex infection, and reduces mortality.

Mycoplasma pneumoniae and Chlamydia pneumoniae in pediatric community-acquired pneumonia: comparative efficacy and safety of clarithromycin vs. erythromycin ethylsuccinate.

We evaluated 260 previously healthy children ages 3 through 12 years who had clinical signs and symptoms of pneumonia, radiographically confirmed. Patients were randomized 1:1 to a 10-day course of either clarithromycin suspension 15 mg/kg/day divided twice a day or erythromycin suspension 40 mg/kg/day divided twice a day or three times a day. Evidence of infection with Chlamydia pneumoniae was detected in 28% (74) of patients: 13% (34) by nasopharyngeal culture and 18% (48) by serology with the microimmunofluorescence assay. Evidence of infection with Mycoplasma pneumoniae was detected in 27% (69) of patients: 20% (53) by nasopharyngeal culture or polymerase chain reaction and 17% (44) by serology with the use of enzyme-linked immunosorbent assay. Serologic confirmation of infection was observed in 23% (8) and 53% (28) of patients with bacteriologically detected C. pneumoniae and M. pneumoniae, respectively. Treatment with clarithromycin vs. erythromycin, respectively, yielded the following outcomes: clinical success 98% (121 of 124) vs. 95% (105 of 110); radiologic success 98% (109 of 111) vs. 94% (92 of 110); and eradication by pathogen, C. pneumoniae 79% (15 of 19) vs. 86% (12 of 14) and M. pneumoniae 100% (9 of 9) vs. 100% (4 of 4). Adverse events were primarily gastrointestinal occurring in almost one-fourth of patients in both groups, and were mild to moderate in severity. Clarithromycin and erythromycin were similarly effective and safe for the treatment of radiographically proved, community-acquired pneumonia in children older than 2 years old.(ABSTRACT TRUNCATED AT 250 WORDS)

Clarithromycin therapy for bacteremic Mycobacterium avium complex disease. A randomized, double-blind, dose-ranging study in patients with AIDS. AIDS Clinical Trials Group Protocol 157 Study Team.

OBJECTIVE: To determine the antimicrobial activity and tolerability of clarithromycin for treating bacteremic Mycobacterium avium complex disease in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A randomized, double-blind, dose-ranging study. SETTING: Outpatient clinics. PATIENTS: 154 patients with human immunodeficiency virus (HIV) infection and blood cultures positive for M. avium complex who had symptomatic disease. INTERVENTIONS: Random assignment to clarithromycin at dosages of 500 mg, 1000 mg, or 2000 mg twice daily for 12 weeks. MAIN OUTCOME MEASURE: Median number of colony-forming units of M. avium complex per milliliter of blood. RESULTS: Clarithromycin decreased mycobacterial CFUs from 2.7 to 2.8 log 10/mL of blood at baseline to less than 0 log 10/mL during follow-up (P < 0.0001). After 2 weeks, patients receiving 500 mg twice daily were less likely to be culture negative than were patients receiving 1000 or 2000 mg twice daily (11% compared with 33% or 29%; P = 0.08). At 6 weeks, the median number of CFUs of M. avium complex/mL of blood was 0 or 1 for all three groups. Clarithromycin-resistant isolates of M. avium complex developed in 46% of patients at a median of 16 weeks. Median survival was longer in patients assigned to 500 mg twice daily (median, 249 days) than in patients assigned to 1000 mg or 2000 mg. Death in the first 12 weeks was lowest in the 500-mg group (P = 0.007). CONCLUSIONS: Clarithromycin therapy acutely decreased M. avium complex bacteremia in patients with HIV infection by more than 99%. Clarithromycin, 500 mg twice daily, was well tolerated and associated with better survival. Emergence of clarithromycin-resistant organisms was an important problem.

Overview of the pharmacology of clarithromycin suspension in children and a comparison with that in adults.

The pharmacokinetics of clarithromycin after oral administration of clarithromycin granules for suspension formulation were investigated in adult volunteers and pediatric patients. A 250-mg single dose study conducted in adults revealed that the extent of absorption of clarithromycin from the suspension formulation was not significantly different from that of the reference tablet formulation, whereas the extent of formation of the active 14-hydroxy (14-OH) metabolite was significantly lower with the suspension formulation. In addition coadministration of the suspension formulation with food did not significantly alter the extent of absorption of clarithromycin or formation of the 14-OH metabolite. A single/multiple dose study conducted in adults revealed a delay in the time to attain peak plasma clarithromycin and 14-OH metabolite concentrations after suspension administration as compared with data obtained after tablet administration in previous studies. Steady state was achieved by Dose 5 in the multiple dose phase (250 mg every 12 hours for seven doses). In addition the mean plasma concentration-vs.-time data after suspension administration compared favorably with that noted after multiple oral dose administration of 250-mg tablets in adults. A single/multiple dose study conducted in pediatric patients revealed that coadministration of the suspension formulation with food did not significantly alter the extent of absorption of clarithromycin or formation of the 14-OH metabolite. During the multiple dose phase (7.5 mg/kg every 12 hours for 4 or 5 days), mean plasma concentration-vs.-time data compared favorably with that noted after multiple oral dose administration of 250-mg and 500-mg tablets in adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Overview of the safety profile of clarithromycin suspension in pediatric patients.

Results of preclinical studies conducted to characterize the safety of clarithromycin oral suspension in juvenile mice, rats and dogs as compared with that in adult animals indicate that there is no enhanced risk in younger animals. Adverse events in these preclinical studies mainly involved decreased body and increased liver and kidney weights. The safety profile of clarithromycin suspension also has been evaluated in Phase II (pharmacokinetic) and III (clinical) United States and international clinical trials conducted in pediatric patients. The most frequently reported adverse events occurring among the 1676 patients studied who received clarithromycin suspension in Phase III trials included diarrhea (7%), vomiting (6%), abdominal pain (2%), headache (2%) and nausea (1%). Adverse events were not serious and were usually rapidly reversible. Adverse event rates did not vary with sex or race. Overall adverse event rates were generally similar to those of comparator beta-lactam suspensions (i.e. amoxicillin, amoxicillin/clavulanate, penicillin VK, cefaclor, cefadroxil). With regard to specific gastrointestinal events, however, clarithromycin was better tolerated than amoxicillin/clavulanate whereas penicillin VK showed a lower incidence of gastrointestinal events. Overall clarithromycin oral suspension appears to be safe and well-tolerated, making it suitable for use in the pediatric population.

Overview of the tolerability profile of clarithromycin in preclinical and clinical trials.

Results of studies conducted to characterise local, systemic, reproductive, and mutagenic effects indicate that the new macrolide antimicrobial clarithromycin is well tolerated within reasonable multiples of the intended clinical dose. No adverse effects of clarithyromycin on male or female fertility, perinatal, or postnatal reproduction were indicated by data from rabbits, mice, rats and macaques. No evidence of mutagenic potential was revealed from various in vitro and in vivo study methodologies. Evidence of low potential for ototoxicity, oculotoxicity, hepatotoxicity and nephrotoxicity was provided in studies involving rats, dogs and primates. In agreement with studies with other macrolides, venous irritation potential for the intravenous lactobionate salt formulation was substantial in rabbit studies. In addition, the safety profile of this agent has been evaluated on the basis of adverse reactions and abnormal laboratory values seen in phase I, II and III international clinical trials conducted in adults. The most frequently reported adverse reactions occurring in 3768 patients receiving clarithromycin in phase II and III trials were nausea (3.8%), diarrhoea (3.0%), abdominal pain (1.9%) and headache (1.7%). Adverse reactions were not serious and were usually rapidly reversible. The incidence of adverse reactions did not vary with gender, race or age. Adverse reaction rates were comparable to or less than those of comparator beta-lactams and macrolides. Overall, clarithromycin appears to be a safe and well-tolerated macrolide antimicrobial agent.

Pharmacokinetics of a clarithromycin suspension in infants and children.

The single- and multiple-dose pharmacokinetics of clarithromycin and its 14-(R)-hydroxylated metabolite in infants and children were studied after oral administration under fasting and nonfasting conditions. Drug absorption appeared to be rapid following a brief delay in its onset; the mean peak concentrations in plasma (Cmax) for clarithromycin were reached within about 3 h under both conditions. The mean Cmax for the parent drug were 3.59 and 4.58 micrograms/ml in single-dose fasting and nonfasting patients, and the respective Cmax for the metabolite were 1.19 and 1.26 micrograms/ml. Data indicate good absorption and no significant effects by food. There was no unusual accumulation in the area under the concentration-time curve and Cmax in the multiple-dose group.

Comparative safety and efficacy of clarithromycin and ampicillin in the treatment of out-patients with acute bacterial exacerbation of chronic bronchitis.

In an open, randomized trial, adult non-hospitalized patients with acute bacterial exacerbation of chronic bronchitis were treated with 500 mg clarithromycin twice daily (n = 53) or 500 mg ampicillin four times daily (n = 50). Causative pathogens included S. pneumoniae, M. catarrhalis, H. influenzae, H. parainfluenzae and S. aureus. For clinically evaluable patients, successful outcome (cure or improvement) was noted for 53/53 (100%) clarithromycin-treated patients and 46/47 (98%) ampicillin-treated patients. Clinically significant improvement in signs and symptoms was comparable between treatment groups. There was 100% bacteriological eradication in both treatment groups. Eight patients (15%) in the clarithromycin group and 10 patients (20%) in the ampicillin group reported adverse events, the majority of which were mild or moderate in severity; six events in each treatment group were digestive-system disorders. The new macrolide, clarithromycin, appears to be effective and well-tolerated in the treatment of acute exacerbation of chronic bronchitis.

Temafloxacin pharmacokinetics in subjects with normal and impaired renal function.

The pharmacokinetics of temafloxacin were investigated following oral administration of single 400-mg doses to 6 normal subjects and 18 subjects with various degrees of impaired renal function. Renal impairment did not significantly affect the peak concentration, time to peak concentration, or the nonrenal clearance of temafloxacin. Both renal clearance (CLR) and total apparent clearance (CLT/F, where F represents the fraction of dose absorbed) of temafloxacin were highly correlated with creatinine clearance (CLCR). The regression equations were as follows: CLR = 0.85.CLCR, with R2 = 0.907, and CLT/F = 56.0 + 0.92.CLCR, with R2 = 0.656. The half-life (mean +/- standard deviation) increased from 10.6 +/- 2.4 h in the normal volunteers to 24.6 +/- 7.3 h in the subjects with a CLCR of less than 10 ml/min; the respective CLT/F decreased from 169 +/- 58 to 70 +/- 27 ml/min. Compared with the CLT/F in the subjects with normal renal function, CLT/F was reduced 60% in subjects with a CLCR of less than 40 ml/min, indicating that the dosage should be reduced by at least one-half for patients with comparable impairment. For the subjects on chronic hemodialysis, most of the variability in the nonrenal clearance and the terminal-phase rate constant of temafloxacin was associated with the quantity of calcium carbonate and related medication taken for the treatment of hyperphosphatemia. Supplemental dosage is not required for patients undergoing hemodialysis, since the distribution of temafloxacin in tissue is extensive and the recoveries from 4-h dialysis sessions accounted for less than 10% of the drug present at the start of the dialysis.

Diagnosis of Giardia lamblia infections by detection of parasite-specific antigens.

Antigen detection methods may facilitate diagnosis of Giardia lamblia in stool specimens. As determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and immunoblotting, G. lamblia cysts and trophozoites share several antigens, especially in the 65-kilodalton and 30- to 34-kilodalton regions. By using blind methods, we compared results obtained by counterimmunoelectrophoresis using cyst-immune rabbit serum and by enzyme-linked immunosorbent assay (ELISA) using trophozoite-immune rabbit serum with results obtained by microscopic examination of a preserved, concentrated, and permanently stained stool specimen. Results were similar when these three methods were used to examine 118 stool specimens from clinical microbiology laboratories (53 specimens with G. lamblia) and specimens from 239 day-care-center toddlers (39 specimens with G. lamblia). Compared with microscopy, we found, for counterimmunoelectrophoresis and ELISA, respectively: sensitivity, 88 versus 94%; specificity, 97 versus 95%; positive predictive value, 86 versus 76%; negative predictive value, 98 versus 97%; and concordance, 89%. The false-positive rate by ELISA was 24% (10 of 42) in day-care-center toddlers but only 3% (1 of 32) in healthy adults (P less than 0.04) as corroborated by microscopy. This discrepancy suggests that the ELISA may be more sensitive than microscopy, which is considered the reference standard, and that results may be dependent, in part, on the epidemiology of the infection in the study subjects.

Prevalence of giardiasis in patients with cystic fibrosis.

A group of 107 patients with cystic fibrosis and a control group of 64 normal members of households of patients with cystic fibrosis were surveyed for Giardia lamblia cysts and trophozoites by counterimmunoelectrophoresis of fecal samples. The patient group had a significantly higher rate of infestation than the control group (28.0% vs 6.3%, P = 0.0006), and the disparity between the two groups increased with age (P = 0.005). Aside from cystic fibrosis, all risk factors examined were without influence, except for the presence of household members less than or equal to 5 years of age. We conclude that our patients with cystic fibrosis have a previously unrecognized increased prevalence of giardiasis compared with that in a control population.